Presentation of airway and general symptoms in COVID‐19 caused by dominant <scp>SARS‐CoV</scp>‐2 variants: A follow‐up on <scp>ARIA</scp> consensus
Authors: Jan Hagemann, Gabrielle Onorato, Christopher Seifen, Sven Becker, Tilman Huppertz, Heidi Olze, Piotr Kuna, Joaquim Mullol, Sanna Toppila Salmi, Joao Fonseca, Philip Rouadi, Torsten Zuberbier, Jean Bousquet, Ludger Klimek
Journal: Allergy (2022)

Several SARS-CoV-2 variants have occurred since the beginning of the COVID-19 pandemic. Mutated variants of concerns (VOC; World Health Organization nomenclature) have a variable contamination rate and virulence. COVID-19 symptoms are polymorphic and vary according to VOC.1 A consensus effort from the ARIA group (Allergic Rhinitis and its Impact on Asthma) has been shown that symptoms from common cold, allergic rhinitis, and COVID-19 are likely to be differentiated in a panel of 15 items.2 Although papers have described major clinical manifestations in these new variants,3, 4 there is no consensus on important symptom changes caused by VOC Delta and Omicron. Following the methods of the first EAACI-ARIA-GA1LEN paper,2 we assessed globally how physicians seeing COVID-19 patients are rating various symptoms induced by different VOC. A bibliographic survey identified common symptoms induced by VOC Delta and Omicron. Then, a Delphi questionnaire regarding key symptoms associated with SARS-CoV-2 infection was developed based on the items from ARIA-EAACI-GA2LEN consensus2 and from literature. Symptoms included common cold (upper airway), chemosensory, bronchial, and pulmonary as well as systemic illness symptoms (Table 1). Participants (not involved in the study design process) were asked to estimate frequency (none, very rare, possible, common, always) and expected symptom intensity (visual analogue scale/VAS, 0 to 10) according to their experience as of March 2022 when seeing VOC Delta and Omicron COVID-19 patients. Wild-type symptom rating was performed in 2020 during the first waves of the pandemic by the same participants. Participants are ARIA airway specialists working in hospitals (in- and outpatient, ICU, and specialty clinic) and/or smaller offices. Statistical analysis (ANOVA/t-test for multiple/two groups) and data analysis were performed through GraphPad Prism (USA). Among 47 questionnaires sent out, 40 were received within 7-day notice. Physicians saw an average of 43.5 COVID-19 patients per month. Responses originated in 26 countries. Symptom intensity differed significantly between wild type and VOC (Figure 1). ANOVA test analyses revealed several significant differences of the symptom intensity between the three variants (Figure 1, left). Nasal symptoms (anterior rhinorrhea, nasal congestion, and pruritus) (p < .001) and sore throat (p < .001) were more pronounced in VOC Omicron, compared to wild type. Olfactory function loss was significantly less marked in VOC Delta and Omicron (p < .001). The same patterns occurred for pulmonary symptoms and signs of severe disease (Figure 1). Symptom intensity also differed significantly between VOC Delta and Omicron for all symptoms mentioned above (p < .01). Significantly differing symptoms were grouped concerning common cold and sore throat, chemosensory, bronchial and pulmonary, as well as systemic (Figure 2). VOC Omicron induce "common cold symptoms" and sore throat more often than wild-type and VOC Delta infections (Figures 2 and 3). Our data from ARIA airway specialists across the globe indicate that VOC Delta and Omicron cause various airway symptoms that significantly differ in terms of intensity and composition to those of wild-type SARS-CoV-2. A recent human challenge study to wild-type virus confirmed none to mild rhinitis symptoms with high proportion of olfactory loss.5 Few studies mostly carried out in the UK showed that sore throat is common with VOC Omicron, whereas chemosensory symptoms were less common.6 A UK-based COVID symptom tracker app "Zoe's Covid Symptom Study" collected millions of symptom samples and showed sore throat, runny nose, sneezing, headache, fever, and persistent cough were the most symptoms in symptoms in VOC Delta.7 The role of vaccination on upper airway symptoms is unclear. Smith et al. found only one symptom alteration over the course of two doses of vaccine, possibly also influenced by alteration of virus strain.8 Initial reports on mRNA vaccines entirely preventing infections are challenged by recent observations by Yochay et al. of high-viral load infections with VOC Omicron, despite multiple previous vaccinations. There are several limitations for our study. Our study is a consensus based on expert opinions. Recall bias due to long intervals between presentations and our study is possible, although small variation in answers supports reliability. These results, for the first time, provide a more global view of the problem. Ultimately, we cannot differentiate here what triggers the effects we have described (vaccination, infections previously experienced by part of the population, other virus properties, etc.), but we do want to provide physicians with a decision-making aid for the current situation. Patients are likely to present variable airway and other symptoms in future that can be misinterpreted as common cold. Thus, the prevention of severe outcomes remains the main goal of current vaccination efforts. Open Access funding enabled and organized by Projekt DEAL. There are no conflicts of interest to declare with regard to this project. The data that support the findings of this study are available from the corresponding author upon reasonable request. Alan Kaplan, International Primary Care Respiratory Group (ICPRG). Antonino Romano, Department of Laboratories/Unit of Pediatrics and Medical Genetics/Allergology, Associazion OASI Maria SS: Troina, Sicilia, IT. Bilun Gemicioglu, Department of Pulmonary Diseases, Cerrahpaşa Faculty of Medicine, İstanbul University-Cerrahpaşa, Istanbul, Turkey. Boleslaw Samoliński, Medical University of Warsaw, Department of the Prevention of Environmental Hazards and Allergology, Warsaw, Poland. Branislawa Milenkovic, Clinic for Pulmonary Disease, University Clinical Center of Serbia, Belgrade, Serbia. Brian Lipworth, Scottish Centre for Respiratory Research, University of Dundee, Scotland. Cemal Cingi, Otolaryngology Department, Eskisehir University, Eskisehir, Turkey. Charlotte Suppli Ulrik, Department of Respiratory Medicine, Copenhagen University Hospital, Denmark. Christian Bergmann, Allergie-Centrum-Charité, Berlin. Désirée Larenas-Linnemann, Centro de Excelenciaen Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico. Dirceu Solé, Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Universidade Federal de Sao Paolo, Brazil. Ewa Jassem, Department of Pulmonology and Allergology, Medical University of Gdansk, Debinki str 7, 90–211 Gdańsk, Poland. Florin Mihaltan. National Institute of Pneumology M Nasta, Bucharest, Romania. Ioanna Tsilligianni, International Primary Care Respiratory Group (ICPRG). Jaime C. Sousa, International Primary Care Respiratory Group (ICPRG). Jaron Zuberbier, Charité Virchow-Klinikum, Humboldt-Universität zu Berlin. Juan Carlos Ivancevich, Department of Allergy and Immunology, Medical Faculty of Universidad del Salvador, Buenos Aires, Argentina. Kimi Okubo, Department of Otolaryngology, Nippon Medical School, Tokyo, Japan. Luis R. Caraballo, Institute for Immunological Research, University of Cartagena, Cartaagena de Indias, Colombia. Maia Gotua, Center of Allergy and Immunology, Tiblisi, Georgia. Mario Zernotti, Department of ENT, Catholic University of Cordoba, Cordoba, Argentina. Mark Dykewicz, Section of Allergy & Immunology, Division of Infectious Diseases, Department of Internal Medicine, St. Louis, USA. Maximiliano Gomez, ALLERGY & ASTHMA UNIT HOSPITAL SAN BERNARDO, SALTA – ARGENTINA. Menachem Rottem, Division of Allergy and Clinical Immunology, Ha'Emek Medical Center, Afula 18,101, Israel. Michael Makris, Allergy Unit, 2nd Dpt. of Dermatology and Venereology, University Hospital Athens, Greece. Motohiro Ebisawa, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan. Musa Khaitov, NRC Institute of Immunology FMBA, Moscow, Russia. Neil Fitch, International Primary Care Respiratory Group (ICPRG). Nelson Augusto Rosario Filho, Department of Pediatrics, Federal University of Parana, Curitiba, PR, Brazil. Neven Miculinic, Croatian Pulmonary Society Zagreb Croatia. Osman Yusef, International Primary Care Respiratory Group (ICPRG). Tari Haahtela, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. Tiago Maricoto, International Primary Care Respiratory Group (ICPRG). Todor A. Popov, University Hospital Sv. Ivan Rilski, Sofia, Bulgaria. Tomohisa Iinuma, Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. Tuula Vasankari, Filhary and University of Turku, Pulmonary diseases and Clinical Allergology, Turku, Finland. Vincenzo Patella, Division of Internal Medicine and Allergy/Immunology, Faculty of Medicine and Surgery, University of Naples Federico II, Naples, Italy. Yoshitaka Okamoto, Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.